%0 Journal Article
%A Da Silva Correia, Angela
%A Laginha, Ines
%A Guimaraes, Susana
%A Dittmar, Kathrin
%A Schmitz, Matthias
%A Castilla, Joaquin
%A Zerr, Inga
%A Silva-Correia, Susana
%T Pedigree analysis and genetic inheritance of fatal familial insomnia (FFI) in a Portuguese multigenerational family.
%J Journal of neurology
%V 272
%N 10
%@ 0367-004X
%C [Darmstadt]
%I Steinkopff
%M DZNE-2025-01183
%P 706
%D 2025
%X Fatal familial insomnia (FFI) is a rare, autosomal dominant prion disease caused by a mutation in the PRNP gene, leading to the misfolding of the cellular prion protein (PrPC) into its pathogenic form (PrPSc). This results in neurodegeneration, particularly in the thalamus, a key region regulating sleep-wake cycles, which underlies the hallmark symptoms of FFI, including insomnia, autonomic dysfunctions, motor disturbances and cognitive decline. This study focuses on a Portuguese family with FFI, providing a detailed pedigree analysis spanning five generations and comprising 134 individuals, to elucidate inheritance patterns, disease onset, and clinical progression. The findings confirm the autosomal-dominant inheritance pattern and a strong familial clustering of the disease with age of onset in the late 50s (mean 57 years). Although 67
%K Humans
%K Insomnia, Fatal Familial: genetics
%K Insomnia, Fatal Familial: physiopathology
%K Male
%K Middle Aged
%K Portugal
%K Female
%K Pedigree
%K Adult
%K Prion Proteins: genetics
%K Aged
%K Age of Onset
%K Disease Progression
%K Extended Family
%K FFI (Other)
%K Fatal familial insomnia (Other)
%K Portugal (Other)
%K PrPC (Other)
%K PrPSc (Other)
%K Prion diseases (Other)
%K Prion Proteins (NLM Chemicals)
%K PRNP protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41107634
%2 pmc:PMC12534306
%R 10.1007/s00415-025-13432-2
%U https://pub.dzne.de/record/281793